This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A myriad of lines of laboratory mice are used as genetic and physiological models of human biology. Researchers use the diversity found in the classical laboratory lines to uncover the genetic basis of complex phenotypes such as disease incidence and behavior (e.g., anxiety). A major limitation of this effort is that the ancestry of classical mouse lines is complex and is thought to involve hybridization between three or four different mouse subspecies from around the globe. This hybridization has resulted in a mosaic of large chromosomal blocks that are derived from single subspecies without recombination. The existence of the block structure has been established in previous research, but it is presently poorly understood. A clear description of the ancestry and chromosomal block sizes in laboratory mice is critical to understanding the limits to mapping phenotypes to individual genes with current mouse lines. As a first step to understanding the ancestry that gave rise to the haplotype structure in recombinant laboratory mouse strains, we are examining the genome structure of several wild-derived mouse strains. Nucleotide sequence data for this project is publicly available. A central hypothesis about the ancestry of classical laboratory lines is that they are the result of hybridization between the house mice Mus musculus castaneus and M. m. musculus (ca. 2000 years ago), which gave rise to M. m. molossinus. In our initial work we are focusing on genomic evidence for the primary hybridization that gave rise to M. m. molossinus.